Article

Mucosal Immunology (2008) 1, 147–155; doi:10.1038/mi.2007.16; published online 23 January 2008

Mast cell production of IL-4 and TNF may be required for protective and pathological responses in gastrointestinal helminth infection

M X Ierna1, H E Scales1, K L Saunders1 and C E Lawrence1

1Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, Scotland

Correspondence: CE Lawrence, (catherine.lawrence@strath.ac.uk)

Received 22 October 2007; Accepted 22 November 2007; Published online 23 January 2008.

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Abstract

Expulsion of the gastrointestinal nematode Trichinella spiralis is associated with Th2 responses and intestinal inflammation, which correlate with a marked mast cell (MC) response. To address the role of MC-derived cytokines in the induction of protective responses, WBB6F1-KitW/KitW-v (W/Wv) mice were reconstituted with wild-type, tumor necrosis factor (TNF)-alpha-/-, or interleukin (IL)-4-/- bone marrow (BM) prior to infection with T. spiralis. W/Wv mice reconstituted with TNF-alpha-/- or IL-4-/- BM expelled the parasite less efficiently and showed diminished enteropathy, whereas protective responses were normal in W/Wv mice reconstituted with wild-type BM and were accompanied by intestinal pathology. MC responses were reduced in W/Wv mice reconstituted with IL-4-/- BM and to a lesser extent when reconstituted with TNF-alpha-/-. These results suggest that MC-derived IL-4 and TNF may regulate the induction of protective Th2 responses and intestinal inflammation associated with the expulsion of T. spiralis. Significantly, these studies suggest a role for MC-derived cytokines as autocrine growth factors.

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